The decline in bone mass with age leads to osteoporosis, a major cause of dissability and morbidity. The basic defect seems to be associated with the unavailability of calcifiable collagen matrix. We have observed that transplantation of syngeneic embryonic cells to very old rats within a osteoinductive resorbable chamber generates bone. Simultaneously we have established significant biochemical and histological differences between true bone formation and dystrophic calcification. We shall continue to investigate the metabolic activities of committed osteogenic and of osteoprogenic cells during the various stages of bone induction. What dictates the presence or absence of cartilage and what is its role in this system? We shall quantitate chondrogenesis using specific markers (collagen types II, 1 alpha, 2 alpha, 3 alpha, IX, X and 35S-labelled proteoglycans). We shall relate these to bone formation for measuring type I collagen and BGP. We shall search for ways to distinguish type I collagen produced by mesenchymal cells and bone cells (i.e. hydroxylysine content of the alpha 2 chain and patterns of glycosylation). We will look for new ways to grow bone cells in vitro, so that they generate a calcifiable matrix, and continue to study the mechanisms of dystrophic calcification and develop animal models to evaluate our potential to enhance bone formation.